HLB's Liver Cancer Drug Rivoceranib Hits Third FDA Setback Over Manufacturing Compliance Issues
Key Insights
HLB's US subsidiary Elevar Therapeutics (search) received a Complete Response Letter from the FDA for Rivoceranib, delaying approval of the liver cancer (search) combination therapy.
The FDA cited manufacturing compliance issues at Jiangsu Hengrui Pharmaceuticals (search)' Chinese facility following a routine cGMP inspection, not deficiencies in clinical efficacy or safety data.
Elevar Therapeutics (search) CEO Kim Dong-gun confirmed no additional clinical trials were requested, and the company plans to work with the FDA toward a rapid resubmission.
HLB Co. (search)'s protracted effort to bring its liver cancer (search) treatment to the US market has encountered yet another regulatory hurdle, as the US Food and Drug Administration issued a Complete Response Letter (CRL) for Rivoceranib, an anti-cancer therapy intended for first-line treatment of liver cancer in combination with Camrelizumab.
The CRL, received by HLB's US subsidiary Elevar Therapeutics (search), stems from observations made during a routine current Good Manufacturing Practice (cGMP) inspection of a manufacturing facility operated by China's Jiangsu Hengrui Pharmaceuticals (search), where Rivoceranib is currently produced. The FDA issued a Form 483 following the April inspection, detailing observations that may indicate deviations from manufacturing standards.
According to HLB, the FDA explained that while the observations may not be directly related to the Rivoceranib application itself, the manufacturing site must address the cited issues before the application can be approved. The agency also stated that approval cannot be granted until the facility demonstrates compliance with cGMP requirements. Depending on the outcome of corrective actions, the FDA may conduct a preapproval inspection (PAI) before making a final decision.
No Clinical Data Concerns
Importantly, the CRL did not raise any issues with the drug's clinical profile. "The CRL does not identify any deficiencies related to the drug's clinical efficacy or safety data, nor does it request additional clinical trials," said Kim Dong-gun, CEO of Elevar Therapeutics (search). "Because the primary issues are related to the manufacturing site's cGMP inspection, we will work closely with the FDA to clarify the necessary procedures and pursue a resubmission as quickly as possible."
HLB noted that this was the first on-site inspection of the Chinese facility since 2018. During the previous five FDA inspections, the site received four "no action indicated" classifications and one "voluntary action indicated" classification. The final classification of the most recent inspection has yet to be determined.
Path Forward
HLB said both the cGMP inspection and any subsequent PAI must produce satisfactory results for the application to proceed. Following receipt of the CRL, Elevar has formally requested that Hengrui provide the Form 483, its responses to the FDA, and a timeline for completing corrective actions. HLB stated it will analyze the FDA's observations and Hengrui's remediation plan before announcing a detailed strategy for resubmitting the application.
The company and Elevar had not been informed in advance of either the routine inspection or the issuance of the Form 483, as the inspection was not conducted as a preapproval inspection tied to the Rivoceranib application.
Market Impact
The latest decision marks the third regulatory setback for HLB's long-running effort to secure FDA approval for Rivoceranib. Shares of HLB plunged by 30% — the lower limit for a stock listed on Korea's secondary tech-heavy bourse Kosdaq — to 36,600 won ($24.21) on the day of the announcement.